摘要
目的探讨非奈利酮对实验性糖尿病肾病大鼠的脂代谢的作用。方法选取24只雄性SPF级SD大鼠,适应性喂养2周后,随机选取6只为正常对照组,给予正常饮食;其余大鼠通过链脲佐菌素和高糖高脂饮食诱导糖尿病肾病模型。造模成功后分为模型组、非奈利酮低/高剂量组(5、10 mg/kg),继续高糖高脂饮食并药物干预。实验结束后腹主动脉采血,检测血脂[总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、游离脂肪酸(FFA)]、氧化应激[过氧化氢酶(CAT)、丙二醛(MDA)、超氧化物歧化酶(SOD)]及炎症因子[白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、脂联素(ADPN)、C反应蛋白(CRP)];取肝肾组织行HE与油红O染色,观察病理变化。结果与正常对照组相比,模型组体重降低(P<0.001),肝脏质量、肝重指数、糖化血红蛋白含量均显著升高(P<0.001);血脂谱指标:TC、LDL-C、FFA和TG升高(P<0.05),HDL-C降低(P<0.001);氧化应激指标:CAT、SOD降低(P<0.001),MDA升高(P<0.001);炎症因子:IL-6、TNF-α、ADPN、CRP升高(P<0.001)。与模型组相比,非奈利酮干预组TC、LDL-C、FFA、MDA、IL-6、TNF-α、ADPN、CRP、ALT、AST均降低(P<0.05),HDL-C、CAT、SOD均升高(P<0.05),肝脏脂沉积得到改善,肾病理状态改变。结论非奈利酮可以下调TC和LDL-C,上调HDL-C,改善糖尿病肾病大鼠的血脂代谢情况,其机制可能和抑制氧化应激和炎症,改善肾小管脂代谢有关。
Objective To investigate the effect of finerenone on lipid metabolism in experimental DKD in rats.Methods A total of 24 male SPF-grade SD rats were acclimatized for 2 weeks.Six rats were randomly selected as the normal control group and given a normal diet.The remaining rats were induced with diabetic kidney disease by administration of streptozotocin combined with a high-fat,high-sugar diet.After successful model establishment,rats were randomly divided into the model group,low-dose finerenone group,and high-dose finerenone group.All rats were given a high-fat,high-sugar diet and drug interventions,with the low-dose and high-dose finerenone groups receiving 5 mg/kg and 10 mg/kg of finerenone,respectively.After the intervention period,blood samples were collected from the abdominal aorta to measure blood lipid profile indicators(total cholesterol[TC],triglyceride[TG],high-density lipoprotein cholesterol[HDL-C],low-density lipoprotein cholesterol[LDL-C],free fatty acid[FFA]),oxidative stress markers(catalase[CAT],malondialdehyde[MDA],superoxide dismutase[SOD]),and inflammatory factors(interleukin-6[IL-6],tumor necrosis factor-α[TNF-α],adiponectin[ADPN],C-reactive protein[CRP]).Liver and kidney tissues were harvested for HE and Oil Red O staining to observe pathological changes.Results Compared to the normal control group,the body weight of the model group was decreased(P<0.001),and the liver weight,liver index,and glycated hemoglobin levels were significantly increased(P<0.001).Blood lipid profile indicators,including TC,LDL-C,FFA,and TG,were significantly elevated(P<0.05),while HDL-C was significantly reduced(P<0.001).Oxidative stress markers,including CAT and SOD,were significantly lower(P<0.001),and MDA levels were significantly higher(P<0.001).Inflammatory factors,including IL-6,TNF-α,ADPN,and CRP,were all significantly elevated(P<0.001).Compared to the model group,finerenone-treated groups showed significant reductions in TC,LDL-C,FFA,MDA,IL-6,TNF-α,ADPN,CRP,ALT,and AST levels(P<0.05),while HDL-C,CAT,and SOD levels were significantly elevated(P<0.05).Liver lipid deposition was improved,and pathological changes in the kidneys were ameliorated.Conclusion Finerenone can improve lipid metabolism in diabetic kidney disease rats by downregulating TC,LDL-C and upregulating HDL-C.The mechanism may involve the inhibition of oxidative stress and inflammation,as well as the improvement of renal tubular lipid metab olism.
作者
何敏
代晶晶
刘炫科
张国锐
杨晓萍
HE Min;DAI Jingjing;LIU Xuanke;ZHANG Guorui;YANG Xiaoping(School of Medicine,Shihezi University,Xinjiang,Shihezi 832003,China;Department of Nephrology,First Affiliated Hospital of Shihezi University,Xinjiang,Shihezi 832003,China)
出处
《中国医药科学》
2025年第16期15-21,75,共8页
China Medicine And Pharmacy
基金
兵团科技计划项目(2022ZD040)
石河子大学科研项目(自然科学)(ZZZC2023052)。
关键词
糖尿病肾病
非奈利酮
炎症
氧化应激
脂代谢
Diabetic kidney disease
Finerenone
Inflammation
Oxidative st ress
Lipid metabolism
